Risk of ovarian cancer and the NF-kB pathway: Genetic association with IL1A and TNFSF10

Bridget Charbonneau; Matthew S. Block; William R. Bamlet; Robert A. Vierkant; Kimberly R. Kalli; Zachary Fogarty; David N. Rider; Thomas A. Sellers; Shelley S. Tworoger; Elizabeth Poole; Harvey A. Risch; Helga B. Salvesen; Lambertus A. Kiemeney; Laura Baglietto; Graham G. Giles; Gianluca Severi; Britton Trabert; Nicolas Wentzensen; Georgia Chenevix-Trench; Alice S. Whittemore; Weiva Sieh; Jenny Chang-Claude; Elisa V. Bandera; Irene Orlow; Kathryn Terry; Marc T. Goodman; Pamela J. Thompson; Linda S. Cook; Mary Anne Rossing; Roberta B. Ness; Steven A. Narod; Jolanta Kupryjanczyk; Karen Lu; Ralf Butzow; Thilo Dork; Tanja Pejovic; Ian Campbell; Nhu D. Le; Clareann H. Bunker; Natalia Bogdanova; Ingo B. Runnebaum; Diana Eccles; James Paul; Anna H. Wu; Simon A. Gayther; Estrid Hogdall; Florian Heitz; Stanley B. Kaye; Beth Y. Karlan; Hoda Anton-Culver; Jacek Gronwald; Claus K. Hogdall; Diether Lambrechts; Peter A. Fasching; Usha Menon; Joellen Schildkraut; Celeste Leigh Pearce; Douglas A. Levine; Susanne Kruger Kjaer; Daniel Cramer; James M. Flanagan; Catherine M. Phelan; Robert Brown; Leon F.A.G. Massuger; Honglin Song; Jennifer A. Doherty; Camilla Krakstad; Dong Liang; Kunle Odunsi; Andrew Berchuck; Allan Jensen; Jan Lubinski; Heli Nevanlinna; Yukie T. Bean; Galina Lurie; Argyrios Ziogas; Christine Walsh; Evelyn Despierre; Louise Brinton; Alexander Hein; Anja Rudolph; Agnieszka Dansonka-Mieszkowska; Sara H. Olson; Philipp Harter; Jonathan Tyrer; Allison F. Vitonis; Angela Brooks-Wilson; Katja K. Aben; Malcolm C. Pike; Susan J. Ramus; Elisabeth Wik; Cezary Cybulski; Jie Lin; Lara Sucheston; Robert Edwards; Valerie McGuire; Jenny Lester; Andreas Du Bois; Lene Lundvall; Shan Wang-Gohrke; Lukasz M. Szafron; Sandrina Lambrechts; Hannah Yang; Matthias W. Beckmann; Liisa M. Pelttari; Anne M. Van Altena; David Van Den Berg; Mari K. Halle; Aleksandra Gentry-Maharaj; Ira Schwaab; Urmila Chandran; Janusz Menkiszak; Arif B. Ekici; Lynne R. Wilkens; Arto Leminen; Francesmary Modugno; Grace Friel; Joseph H. Rothstein; Ignace Vergote; Montserrat Garcia-Closas; Michelle A.T. Hildebrandt; Piotr Sobiczewski; Linda E. Kelemen; Paul D.P. Pharoah; Kirsten Moysich; Keith L. Knutson; Julie M. Cunningham; Brooke L. Fridley; Ellen L. Goode

doi:10.1158/0008-5472.CAN-13-1051

Risk of ovarian cancer and the NF-kB pathway: Genetic association with IL1A and TNFSF10

Bridget Charbonneau, Matthew S. Block, William R. Bamlet, Robert A. Vierkant, Kimberly R. Kalli, Zachary Fogarty, David N. Rider, Thomas A. Sellers, Shelley S. Tworoger, Elizabeth Poole, Harvey A. Risch, Helga B. Salvesen, Lambertus A. Kiemeney, Laura Baglietto, Graham G. Giles, Gianluca Severi, Britton Trabert, Nicolas Wentzensen, Georgia Chenevix-Trench, Alice S. WhittemoreWeiva Sieh, Jenny Chang-Claude, Elisa V. Bandera, Irene Orlow, Kathryn Terry, Marc T. Goodman, Pamela J. Thompson, Linda S. Cook, Mary Anne Rossing, Roberta B. Ness, Steven A. Narod, Jolanta Kupryjanczyk, Karen Lu, Ralf Butzow, Thilo Dork, Tanja Pejovic, Ian Campbell, Nhu D. Le, Clareann H. Bunker, Natalia Bogdanova, Ingo B. Runnebaum, Diana Eccles, James Paul, Anna H. Wu, Simon A. Gayther, Estrid Hogdall, Florian Heitz, Stanley B. Kaye, Beth Y. Karlan, Hoda Anton-Culver, Jacek Gronwald, Claus K. Hogdall, Diether Lambrechts, Peter A. Fasching, Usha Menon, Joellen Schildkraut, Celeste Leigh Pearce, Douglas A. Levine, Susanne Kruger Kjaer, Daniel Cramer, James M. Flanagan, Catherine M. Phelan, Robert Brown, Leon F.A.G. Massuger, Honglin Song, Jennifer A. Doherty, Camilla Krakstad, Dong Liang, Kunle Odunsi, Andrew Berchuck, Allan Jensen, Jan Lubinski, Heli Nevanlinna, Yukie T. Bean, Galina Lurie, Argyrios Ziogas, Christine Walsh, Evelyn Despierre, Louise Brinton, Alexander Hein, Anja Rudolph, Agnieszka Dansonka-Mieszkowska, Sara H. Olson, Philipp Harter, Jonathan Tyrer, Allison F. Vitonis, Angela Brooks-Wilson, Katja K. Aben, Malcolm C. Pike, Susan J. Ramus, Elisabeth Wik, Cezary Cybulski, Jie Lin, Lara Sucheston, Robert Edwards, Valerie McGuire, Jenny Lester, Andreas Du Bois, Lene Lundvall, Shan Wang-Gohrke, Lukasz M. Szafron, Sandrina Lambrechts, Hannah Yang, Matthias W. Beckmann, Liisa M. Pelttari, Anne M. Van Altena, David Van Den Berg, Mari K. Halle, Aleksandra Gentry-Maharaj, Ira Schwaab, Urmila Chandran, Janusz Menkiszak, Arif B. Ekici, Lynne R. Wilkens, Arto Leminen, Francesmary Modugno, Grace Friel, Joseph H. Rothstein, Ignace Vergote, Montserrat Garcia-Closas, Michelle A.T. Hildebrandt, Piotr Sobiczewski, Linda E. Kelemen, Paul D.P. Pharoah, Kirsten Moysich, Keith L. Knutson, Julie M. Cunningham, Brooke L. Fridley, Ellen L. Goode

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1a (IL1A) is both regulated by and able to activate NF-kB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-kB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76-0.93; P < 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P < 0.006). Considering a multiple-testing-corrected significance threshold of P < 2.5 ± 10-5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P < 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted.

Original language	English (US)
Pages (from-to)	852-861
Number of pages	10
Journal	Cancer research
Volume	74
Issue number	3
DOIs	https://doi.org/10.1158/0008-5472.CAN-13-1051
State	Published - Feb 1 2014

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1158/0008-5472.CAN-13-1051

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Charbonneau, B., Block, M. S., Bamlet, W. R., Vierkant, R. A., Kalli, K. R., Fogarty, Z., Rider, D. N., Sellers, T. A., Tworoger, S. S., Poole, E., Risch, H. A., Salvesen, H. B., Kiemeney, L. A., Baglietto, L., Giles, G. G., Severi, G., Trabert, B., Wentzensen, N., Chenevix-Trench, G., ... Goode, E. L. (2014). Risk of ovarian cancer and the NF-kB pathway: Genetic association with IL1A and TNFSF10. Cancer research, 74(3), 852-861. https://doi.org/10.1158/0008-5472.CAN-13-1051

Charbonneau, B, Block, MS, Bamlet, WR, Vierkant, RA, Kalli, KR, Fogarty, Z, Rider, DN, Sellers, TA, Tworoger, SS, Poole, E, Risch, HA, Salvesen, HB, Kiemeney, LA, Baglietto, L, Giles, GG, Severi, G, Trabert, B, Wentzensen, N, Chenevix-Trench, G, Whittemore, AS, Sieh, W, Chang-Claude, J, Bandera, EV, Orlow, I, Terry, K, Goodman, MT, Thompson, PJ, Cook, LS, Rossing, MA, Ness, RB, Narod, SA, Kupryjanczyk, J, Lu, K, Butzow, R, Dork, T, Pejovic, T, Campbell, I, Le, ND, Bunker, CH, Bogdanova, N, Runnebaum, IB, Eccles, D, Paul, J, Wu, AH, Gayther, SA, Hogdall, E, Heitz, F, Kaye, SB, Karlan, BY, Anton-Culver, H, Gronwald, J, Hogdall, CK, Lambrechts, D, Fasching, PA, Menon, U, Schildkraut, J, Pearce, CL, Levine, DA, Kjaer, SK, Cramer, D, Flanagan, JM, Phelan, CM, Brown, R, Massuger, LFAG, Song, H, Doherty, JA, Krakstad, C, Liang, D, Odunsi, K, Berchuck, A, Jensen, A, Lubinski, J, Nevanlinna, H, Bean, YT, Lurie, G, Ziogas, A, Walsh, C, Despierre, E, Brinton, L, Hein, A, Rudolph, A, Dansonka-Mieszkowska, A, Olson, SH, Harter, P, Tyrer, J, Vitonis, AF, Brooks-Wilson, A, Aben, KK, Pike, MC, Ramus, SJ, Wik, E, Cybulski, C, Lin, J, Sucheston, L, Edwards, R, McGuire, V, Lester, J, Du Bois, A, Lundvall, L, Wang-Gohrke, S, Szafron, LM, Lambrechts, S, Yang, H, Beckmann, MW, Pelttari, LM, Van Altena, AM, Van Den Berg, D, Halle, MK, Gentry-Maharaj, A, Schwaab, I, Chandran, U, Menkiszak, J, Ekici, AB, Wilkens, LR, Leminen, A, Modugno, F, Friel, G, Rothstein, JH, Vergote, I, Garcia-Closas, M, Hildebrandt, MAT, Sobiczewski, P, Kelemen, LE, Pharoah, PDP, Moysich, K, Knutson, KL , Cunningham, JM, Fridley, BL & Goode, EL 2014, 'Risk of ovarian cancer and the NF-kB pathway: Genetic association with IL1A and TNFSF10', Cancer research, vol. 74, no. 3, pp. 852-861. https://doi.org/10.1158/0008-5472.CAN-13-1051

@article{0692a01662e14473898e37a92c916e47,

title = "Risk of ovarian cancer and the NF-kB pathway: Genetic association with IL1A and TNFSF10",

abstract = "A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1a (IL1A) is both regulated by and able to activate NF-kB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-kB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76-0.93; P < 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P < 0.006). Considering a multiple-testing-corrected significance threshold of P < 2.5 ± 10-5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P < 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted.",

author = "Bridget Charbonneau and Block, {Matthew S.} and Bamlet, {William R.} and Vierkant, {Robert A.} and Kalli, {Kimberly R.} and Zachary Fogarty and Rider, {David N.} and Sellers, {Thomas A.} and Tworoger, {Shelley S.} and Elizabeth Poole and Risch, {Harvey A.} and Salvesen, {Helga B.} and Kiemeney, {Lambertus A.} and Laura Baglietto and Giles, {Graham G.} and Gianluca Severi and Britton Trabert and Nicolas Wentzensen and Georgia Chenevix-Trench and Whittemore, {Alice S.} and Weiva Sieh and Jenny Chang-Claude and Bandera, {Elisa V.} and Irene Orlow and Kathryn Terry and Goodman, {Marc T.} and Thompson, {Pamela J.} and Cook, {Linda S.} and Rossing, {Mary Anne} and Ness, {Roberta B.} and Narod, {Steven A.} and Jolanta Kupryjanczyk and Karen Lu and Ralf Butzow and Thilo Dork and Tanja Pejovic and Ian Campbell and Le, {Nhu D.} and Bunker, {Clareann H.} and Natalia Bogdanova and Runnebaum, {Ingo B.} and Diana Eccles and James Paul and Wu, {Anna H.} and Gayther, {Simon A.} and Estrid Hogdall and Florian Heitz and Kaye, {Stanley B.} and Karlan, {Beth Y.} and Hoda Anton-Culver and Jacek Gronwald and Hogdall, {Claus K.} and Diether Lambrechts and Fasching, {Peter A.} and Usha Menon and Joellen Schildkraut and Pearce, {Celeste Leigh} and Levine, {Douglas A.} and Kjaer, {Susanne Kruger} and Daniel Cramer and Flanagan, {James M.} and Phelan, {Catherine M.} and Robert Brown and Massuger, {Leon F.A.G.} and Honglin Song and Doherty, {Jennifer A.} and Camilla Krakstad and Dong Liang and Kunle Odunsi and Andrew Berchuck and Allan Jensen and Jan Lubinski and Heli Nevanlinna and Bean, {Yukie T.} and Galina Lurie and Argyrios Ziogas and Christine Walsh and Evelyn Despierre and Louise Brinton and Alexander Hein and Anja Rudolph and Agnieszka Dansonka-Mieszkowska and Olson, {Sara H.} and Philipp Harter and Jonathan Tyrer and Vitonis, {Allison F.} and Angela Brooks-Wilson and Aben, {Katja K.} and Pike, {Malcolm C.} and Ramus, {Susan J.} and Elisabeth Wik and Cezary Cybulski and Jie Lin and Lara Sucheston and Robert Edwards and Valerie McGuire and Jenny Lester and {Du Bois}, Andreas and Lene Lundvall and Shan Wang-Gohrke and Szafron, {Lukasz M.} and Sandrina Lambrechts and Hannah Yang and Beckmann, {Matthias W.} and Pelttari, {Liisa M.} and {Van Altena}, {Anne M.} and {Van Den Berg}, David and Halle, {Mari K.} and Aleksandra Gentry-Maharaj and Ira Schwaab and Urmila Chandran and Janusz Menkiszak and Ekici, {Arif B.} and Wilkens, {Lynne R.} and Arto Leminen and Francesmary Modugno and Grace Friel and Rothstein, {Joseph H.} and Ignace Vergote and Montserrat Garcia-Closas and Hildebrandt, {Michelle A.T.} and Piotr Sobiczewski and Kelemen, {Linda E.} and Pharoah, {Paul D.P.} and Kirsten Moysich and Knutson, {Keith L.} and Cunningham, {Julie M.} and Fridley, {Brooke L.} and Goode, {Ellen L.}",

year = "2014",

month = feb,

day = "1",

doi = "10.1158/0008-5472.CAN-13-1051",

language = "English (US)",

volume = "74",

pages = "852--861",

journal = "Cancer research",

issn = "0008-5472",

publisher = "American Association for Cancer Research Inc.",

number = "3",

}

TY - JOUR

T1 - Risk of ovarian cancer and the NF-kB pathway

T2 - Genetic association with IL1A and TNFSF10

AU - Charbonneau, Bridget

AU - Block, Matthew S.

AU - Bamlet, William R.

AU - Vierkant, Robert A.

AU - Kalli, Kimberly R.

AU - Fogarty, Zachary

AU - Rider, David N.

AU - Sellers, Thomas A.

AU - Tworoger, Shelley S.

AU - Poole, Elizabeth

AU - Risch, Harvey A.

AU - Salvesen, Helga B.

AU - Kiemeney, Lambertus A.

AU - Baglietto, Laura

AU - Giles, Graham G.

AU - Severi, Gianluca

AU - Trabert, Britton

AU - Wentzensen, Nicolas

AU - Chenevix-Trench, Georgia

AU - Whittemore, Alice S.

AU - Sieh, Weiva

AU - Chang-Claude, Jenny

AU - Bandera, Elisa V.

AU - Orlow, Irene

AU - Terry, Kathryn

AU - Goodman, Marc T.

AU - Thompson, Pamela J.

AU - Cook, Linda S.

AU - Rossing, Mary Anne

AU - Ness, Roberta B.

AU - Narod, Steven A.

AU - Kupryjanczyk, Jolanta

AU - Lu, Karen

AU - Butzow, Ralf

AU - Dork, Thilo

AU - Pejovic, Tanja

AU - Campbell, Ian

AU - Le, Nhu D.

AU - Bunker, Clareann H.

AU - Bogdanova, Natalia

AU - Runnebaum, Ingo B.

AU - Eccles, Diana

AU - Paul, James

AU - Wu, Anna H.

AU - Gayther, Simon A.

AU - Hogdall, Estrid

AU - Heitz, Florian

AU - Kaye, Stanley B.

AU - Karlan, Beth Y.

AU - Anton-Culver, Hoda

AU - Gronwald, Jacek

AU - Hogdall, Claus K.

AU - Lambrechts, Diether

AU - Fasching, Peter A.

AU - Menon, Usha

AU - Schildkraut, Joellen

AU - Pearce, Celeste Leigh

AU - Levine, Douglas A.

AU - Kjaer, Susanne Kruger

AU - Cramer, Daniel

AU - Flanagan, James M.

AU - Phelan, Catherine M.

AU - Brown, Robert

AU - Massuger, Leon F.A.G.

AU - Song, Honglin

AU - Doherty, Jennifer A.

AU - Krakstad, Camilla

AU - Liang, Dong

AU - Odunsi, Kunle

AU - Berchuck, Andrew

AU - Jensen, Allan

AU - Lubinski, Jan

AU - Nevanlinna, Heli

AU - Bean, Yukie T.

AU - Lurie, Galina

AU - Ziogas, Argyrios

AU - Walsh, Christine

AU - Despierre, Evelyn

AU - Brinton, Louise

AU - Hein, Alexander

AU - Rudolph, Anja

AU - Dansonka-Mieszkowska, Agnieszka

AU - Olson, Sara H.

AU - Harter, Philipp

AU - Tyrer, Jonathan

AU - Vitonis, Allison F.

AU - Brooks-Wilson, Angela

AU - Aben, Katja K.

AU - Pike, Malcolm C.

AU - Ramus, Susan J.

AU - Wik, Elisabeth

AU - Cybulski, Cezary

AU - Lin, Jie

AU - Sucheston, Lara

AU - Edwards, Robert

AU - McGuire, Valerie

AU - Lester, Jenny

AU - Du Bois, Andreas

AU - Lundvall, Lene

AU - Wang-Gohrke, Shan

AU - Szafron, Lukasz M.

AU - Lambrechts, Sandrina

AU - Yang, Hannah

AU - Beckmann, Matthias W.

AU - Pelttari, Liisa M.

AU - Van Altena, Anne M.

AU - Van Den Berg, David

AU - Halle, Mari K.

AU - Gentry-Maharaj, Aleksandra

AU - Schwaab, Ira

AU - Chandran, Urmila

AU - Menkiszak, Janusz

AU - Ekici, Arif B.

AU - Wilkens, Lynne R.

AU - Leminen, Arto

AU - Modugno, Francesmary

AU - Friel, Grace

AU - Rothstein, Joseph H.

AU - Vergote, Ignace

AU - Garcia-Closas, Montserrat

AU - Hildebrandt, Michelle A.T.

AU - Sobiczewski, Piotr

AU - Kelemen, Linda E.

AU - Pharoah, Paul D.P.

AU - Moysich, Kirsten

AU - Knutson, Keith L.

AU - Cunningham, Julie M.

AU - Fridley, Brooke L.

AU - Goode, Ellen L.

PY - 2014/2/1

Y1 - 2014/2/1

N2 - A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1a (IL1A) is both regulated by and able to activate NF-kB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-kB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76-0.93; P < 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P < 0.006). Considering a multiple-testing-corrected significance threshold of P < 2.5 ± 10-5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P < 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted.

AB - A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1a (IL1A) is both regulated by and able to activate NF-kB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-kB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76-0.93; P < 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P < 0.006). Considering a multiple-testing-corrected significance threshold of P < 2.5 ± 10-5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P < 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted.

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UR - http://www.scopus.com/inward/citedby.url?scp=84893837618&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-13-1051

DO - 10.1158/0008-5472.CAN-13-1051

M3 - Article

C2 - 24272484

AN - SCOPUS:84893837618

SN - 0008-5472

VL - 74

SP - 852

EP - 861

JO - Cancer research

JF - Cancer research

IS - 3

ER -

Risk of ovarian cancer and the NF-kB pathway: Genetic association with IL1A and TNFSF10

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